Study Suggests Breast Cancer Screening Options for Women With ATM, CHEK2, and PALB2 Mutations
Women who have a higher risk of breast cancer because of a mutation in the ATM, CHEK2, or PALB2 genes would likely benefit from starting annual breast cancer screening with MRI between the ages of 30 and 35 and an annual MRI and mammogram starting at age 40, according to a simulation modeling study.
The research was published online on Feb. 17, 2022, by the journal JAMA Oncology. Read the abstract of “Breast Cancer Screening Strategies for Women With ATM, CHEK2, and PALB2 Pathogenic Variants: A Comparative Modeling Analysis.”
About 5% to 10% of breast cancers are thought to be hereditary, caused by mutations in certain genes passed from parent to child.
Two of the most well-known genes that can mutate and raise the risk of breast and ovarian cancer are BRCA1 and BRCA2. Women who inherit a mutation in either of these genes — from their mothers or fathers — have a much higher-than-average risk of developing breast cancer and ovarian cancer.
The average woman’s risk of developing breast cancer in her lifetime is about 13%. According to the National Cancer Institute (NCI), women with a BRCA1 mutation have between a 55% and 72% lifetime risk of developing breast cancer, and women with a BRCA2 mutation have between a 45% and 69% lifetime risk of developing breast cancer.
Still, there are other genetic mutations that can increase breast cancer risk. Research suggests that mutations in the ATM, CHEK2, and PALB2 genes can double breast cancer risk. Although not as common as BRCA mutations, these mutations have been found in 2% to 3% of women diagnosed with breast cancer. Breast cancer screening recommendations for women who carry ATM, CHEK2, or PALB2 mutations haven’t been established because they don’t increase risk as much as BRCA mutations.
About the study
In this study, the researchers used simulation models from the Cancer Intervention and Surveillance Modeling Network (CISNET). CISNET is a group of NCI-sponsored researchers who use simulation modeling to improve our understanding of cancer prevention, screening, and treatment options, and to see how these strategies affect the number of cancer cases and cancer outcomes.
Scientists have used CISNET simulation models to help develop screening guidelines for the U.S. Preventive Services Task Force and the American Cancer Society.
For this study, the researchers used CISNET breast cancer simulation models to analyze the benefits and risks of starting breast cancer screening with MRI and mammography at age 25, 30, 35, or 40 and continuing until age 74 for women with ATM, CHEK2, or PALB2 gene mutations.
fewer breast cancer deaths, which led to overall lower breast cancer mortality
years of life gained by women because breast cancer was diagnosed and treated
false-positive screening results
biopsies that found no cancer, called benign biopsies by the researchers
When a breast cancer screening test shows a suspicious area that looks like — but isn’t — cancer, it’s called a false positive. Ultimately the news is good: no breast cancer. But the suspicious area usually requires follow-up with more than one doctor as well as extra tests and procedures, sometimes including a biopsy. There are psychological, physical, and economic costs that come with a false positive.
The models estimated the average lifetime breast cancer risk was:
20.9% for women with an ATM mutation
27.6% for women with a CHEK2 mutation
39.5% for women with a PALB2 mutation
The benefits and risks by screening option per 1,000 women screened are as follows:
Annual mammogram starting at age 40: The analysis estimated that having a mammogram each year starting at age 40 would reduce breast cancer mortality by 36.4% to 38.5% versus no screening at all. This screening option would lead to between 13.3 and 29.7 fewer breast cancer deaths. It also would lead to between 2,092 and 2,224 false-positive results as well as between 279 and 296 benign biopsies.
Annual mammogram and MRI starting at age 40: The analysis estimated that a mammogram and MRI each year starting at age 40 would reduce breast cancer mortality
by 52.3% to 53.6% versus no screening at all. This screening option would lead to between 18.4 and 42.4 fewer breast cancer deaths. It also would lead to between 4,233 and 4,569 false-positive results as well as between 1,109 and 1,196 benign biopsies.
Annual MRI from ages 25 to 39 and annual MRI and mammogram starting at age 40: The analysis estimated that an MRI each year from ages 25 to 39 and an annual MRI and mammogram starting at age 40 would reduce breast cancer mortality by 55.7% to 60.2% versus no screening at all. This screening option would lead to between 20.5 and 45 fewer breast cancer deaths. It also would lead to between 5,592 and 5,932 false-positive results as well as between 1,637 and 1,725 benign biopsies.
The researchers defined an option as more efficient if it had comparatively fewer false-positive results and benign biopsies. The results showed that annual MRI screening from ages 35 to 39 and an annual MRI and mammogram from ages 40 to 74 was more efficient than an annual mammogram and MRI from ages 40 to 74. Starting MRI screening at age 30 instead of age 35 also was more efficient than an annual mammogram starting at age 40. But starting MRI screening at age 25 was less efficient than starting MRI screening at age 30.
“Based on our results, annual MRI screening starting at age 30 to 35 years followed by combined annual MRI and mammography at age 40 years likely offers the best balance of screening benefits and harms,” the researchers wrote. “Starting mammography earlier than 40 years increased false-positive screenings and benign biopsies but added little benefit for women receiving MRI.”
What this means for you
If you know you have a higher-than-average risk of breast cancer because of a mutation in the ATM, CHEK2, or PALB2 genes, it makes sense to talk to your doctor about starting annual breast cancer screening in your 30s with tests such as MRI or ultrasound.
This study found that starting screening between the ages of 30 and 35 with an annual MRI and adding an annual mammogram starting at age 40 offered the most benefits and fewest risks. But this screening option has not been officially recommended for women with ATM, CHEK2, or PALB2 mutations.
You can be your own best advocate and talk with your doctor about whether earlier screening makes sense for your unique situation.
Learn more about genetic mutations linked to a higher risk of breast cancer.
Learn more about breast cancer screening tests.
Written by: Jamie DePolo, senior editor
— Last updated on April 1, 2022, 2:22 PM